Is septic shock without lactate elevation as sick as those with? This retrospective study would say they are not. Maybe the alactemic septic patient can just be fluid resuscitated and get their pressors without having to worry about going further. [2. J Crit Care 2011;26:435] [3. Crit Care Res Pract. 2012;2012:536852]

Nguyen’s Asian quality improvement trial added lactate clearance to standard EGDT. These patients were hemodynamically stable with normal ScvO2 and good fluid loading before trial entrance. After multi-variate analysis, patients who cleared lactate had lower risk of death than those who did not. [2. Nguyen HB et al. Outcome Effectiveness of the severe sepsis resuscitation bundle with the addition of lactate clearance as a bundle item: a multi-national evaluation. Crit Care 2011;15:R229]

2nd RCT: A prospective, randomized controlled trial was performed involving 273 patients in the early stage of shock at risk of potential MODS development.

The incidence of MODS in the EGDT group was significantly lower than that in control group (P=0.002). The Lactate(2), Lactate(4), SOFA(T), SOFA(S), and the number of dysfunctional organs in EGDT group were also significantly lower (P=0.045, 0.016, 0.009, 0.010, 0.002). EGDT was associated with a significantly lower total mortality rate of MODS than the conventional therapy (P=0.007), and also with a significantly lower mortality rate of MODS after controlling for severe sepsis (P=0.047 and 0.044)[1. Chen ZQ, Jin YH, Chen H, Fu WJ, Yang H, Wang RT. Early goal-directed therapy lowers the incidence, severity and mortality of multiple organ dysfunction syndrome. Nan Fang Yi Ke Da Xue Xue Bao. 2007 Dec;27(12):1892-5.]

A point counterpoint debate with Rivers from Chest. [1. Rivers EP. Point: adherence to early goal-directed therapy: does it really matter? Yes. After a decade, the scientific proof speaks for itself. Chest. 2010 Sep;138(3):476?80;discussion 484-5.]

One argument to continue to use invasive strategy is that lactate may not detect low, but persistent levels of oxygen debt. [22. Crit Care Med 2004;32:1825]

Reanalysis of the Jones trial shows ScvO2 clearance did not have as good a mortality benefit as lactate clearance, but remember; very view patients needed anything more that fluids/pressors in this trial [11. Puskarich et al. Prognostic Value and Agreement of Achieving Lactate Clearance or Central Venous Oxygen Saturation Goals During Early Sepsis Resuscitation. Acad Emerg Med 2012;19:252]

Alactemic Sepsis

In this study, 9.1% of the hypotensive patients had a lactate < 2 and 24.2% had a lactate < 4. [1. Na S. Implementation of a 6-hour severe sepsis bundle in multiple asian countries is associated with decreased mortality. Chest. 2009;136: 20S.]

In this second study, 11.6% of the patients had the lactate <2 and 25% had lactates <4 [2. Cannon CM. The GENESIS Project (GENeralization of Early Sepsis InterventionS): A Multicenter Quality Improvement Collaborative.]

Cryptic (Occult) Sepsis

In abstract form, this demonstrated that the cryptic shock patients probably got the lion’s share of mortality benefit as opposed to the patients that were already on the downslope. [1. Donnino MW. Cryptic Septic Shock: A Sub-analysis of Early, Goal-Directed Therapy http://meeting.chestpubs.org/cgi/content/abstract/124/4/90S-b]

In a newly published study, they compared cryptic and overt shock patients; the mortality between the two groups was the same. This was a reanalysis of the Jones paper. Of interest, many of the patients in the Occult Shock group had lactates < 4; are these patients less sick? [1. Resuscitation 2011;82:1289]

If antibiotics were delayed until after shock recognition, severe sepsis patients did markedly worse. Delay for patients not in shock did not seem to have an effect on mortality [4. Puskarich et al. Crit Care Med 2011;39:2066]

Source Control

Vasopressor Choice

De Backer’s Meta-Analysis of dopamine vs. norepi, may be the final piece in making norepi the 1st choice pressor for sepsis [1. CCM 2012;40:725]

RBC Transfusion

Small study only capable of suggesting hypotheses: In patients with Hb 6-8, transfusion improved micro-dialysis assessed lactate/pyruvate ratio. But some patients improved and some got worse. Patients with bad L/P pretransfusion were most likely to improve with transfusion. (Intensive Care Med 2012;38:1843)

Misc.

Still patient benefit even if we miss the 6-hour time window for bundle completion [1. Shock 2011;36(6):542]

When we look at the microcirculation, some patients will actually benefit from MAPs of >65. They used NE and pushed MAP to 85 mm Hg and then checked micro-circ effects with NIRS and SDF [1. Crit Care 2011;15:R222]

Proof of my contention of Denominator Shift Bias

Regulatory Crap

Bibliography

Comments

I am interested in any feedback you may have on the use of ketamine drips for sedation in the setting of severe sepsis. I have been using fentanyl drips for sedation in a variety of settings with success. I would think that ketamine would be an ideal sedative adjunct with severe sepsis. Any information or feedback to support the use of ketamine in this setting is appreciated.

scott you said sepsis protocol result in 12 percent mortality reduction. Do the patients who die of sepsis in your protocol suffer longer. For example do they stay longer in ICU. Do they end up receiving more invasive interventions?

If more people are cured AND those that die do so more humanely, than your protocol should be adapted widely. I will cast my net wide.

If those that die survive weeks in ICU instead of hours; the protocol might benefit from some exclusion criteria. I will cast the net more selectively.

The triage screening tool seems very liberal. During a bad flu season there are days when it seems as if everyone meets SIRS criteria. Several otherwise healthy people with the flu or URI would might be getting an invasive and unnecessary screening work-up. Then what to do with the young person, mildly malaised but non-toxic, flu positive with a white count of 18k, creatinine/BUN of 1.4/30 and a lactate of 3.0?

That was our intent. All a positive screen gets you is a lactate sent; there is no reason not to be liberal on the screen. In your pt you mention with a lactate of 3, what do you do? You do exactly what you would have done without a lactate. Flu does cause severe sepsis though and a patient with a lactate of 5 is probably staying in-house b/c they might be one of the many who will decompensate like the ones we have been seeing this flu season.

i’m getting lots of grumblings about initiating a sepsis triage screening tool without a formal wbc count because i suspect it doesn’t identically match sirs criteria. clearly it fails to become a triage screening tool if laboratory data is included. any true evidence based on excluding the wbc count beyond what i would describe as obvious logic. thanks. anyone’s thoughts would be appreciated. thanks. cjh

I think the grumblers are missing the point, the GNYHA screen is more sensitive not less. We haven’t published yet, but we have >15,000 patients now and the screen has found the severe sepsis patients at our participating hospitals. What I would tell these folks is do the triage screen, and then if a patient screens negative, the docs or PAs or NPs will get back the white count and they can reeval if they want to send a lactate.

There are 3 major RCT’s questioning the whole Rivers Protocol. One is ARISE trial from the ANZICS group and Process trial funded by NIH from University of Pittsburgh as well as one in the UK. There is evidence that excess fluid titrated to CVP increases mortality and if one is Rivers purist one should aim for Hgb of >10 in some of these situations (not 7-10). though major RCT shows no benefit from tx >7.0 hgb in most cases. Also some studies have shown dobutamine increases mortality in sepsis. No one argues with early aggressive fluids and keeping MAP. The value of the protocol and interventions is questioned by many reputable physicians. I am happy to send reference list if desired.

Harry,
You may want to listen to some of the recent casts on the subject. I am not a proponent of classic EGDT, but that being said:
There is NO evidence that fluid titrated to CVP increases mortality
There is no evidence that a Hb trigger of 10 has no benefit IN THESE PATIENTS.
No study shows dobutamine increases mortality when titrated to non-supranormal goals.
We may want to separate out the associations from causative evidence when we make this case.

Agee with dobutamine as harm only shown for supranormal. However if titrtae to mixed venous alone one may overshoot. Agree that not clear if harm in this subset by hgb 10 but the only RCT has not shown benefit. There is a retrospective study showing better mortaility with CVP<8 as opposed to 8-12 based on VASST study admittedly it is not an RCT- Crit care Med 2011 Vol 39 #2 p259-265. Thanks and do overall like the modfied rivers approach yu have on the site. Thanks

Scott,
Apologies that this comment is late in the game..Hopefully you’ll see it and can give some advice.
We are just now (better late than never..) implementing system wide protocols for early screening and treatment protocols for sepsis. I’ve been tasked with the staff education part and have relied heavily on your work with the NY collaborative. We are advocating simultaneous antibiotic administration for our ED nurses. However, the some of the nursing staff appear to be suffering from “paradigm paralysis” as sequential antibiotic administration has been a dogma long taught in nursing school “in order to know which antibiotic might cause a reaction”. Is there literature that discusses the actual percentage of antibiotic reactions so I can help shift their paradigm? Do you have any other practical advice to help with this barrier?
Thanks so much Scott,
Aaron

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Who am I?

Hi, my name is Scott Weingart. I am an ED
Intensivist from New York City. My career goal and the purpose of this blog and podcast is to bring Upstairs Care, Downstairs-–that is to bring ICU level care to the ED, so our patients can receive optimum treatment the moment they roll through the door.